Project Summary The goal of this proposal is to secure funds to support the 1st International SYNGAP1 Conference. MRD5 (MIM#: 612621; www.omim.org/entry/612621) is a recently discovered sporadic form of intellectual disability (ID). This disorder is caused by deleterious de novo mutations in the SYNGAP1 gene, which encodes the synaptic RasGAP, SynGAP. Symptoms of MRD5 include cognitive impairment and severely impaired expressive and receptive language. Epilepsy, ASD and ADHD are common comorbid conditions often described in these patients. Pathogenic mutations in SYNGAP1 are surprisingly common, with the incidence reported as 1-4/10,000 individuals, or approximately 1-2% of all ID cases, making it one of the most common genetic causes of ID. It is crucial in the case of SYNGAP1 to have an international meeting bringing together all relevant stakeholders (i.e. patient families, clinicians and researchers) because so little is understood about this emerging brain disorder. While it is known that SynGAP protein is critical for regulating learning and neural excitability in both humans and mice, it remains unclear how loss of functional SynGAP protein leads to symptoms of the disorder. Furthermore, there is a general lack of awareness of the disease, resulting in delay of diagnosis and there is no centralized location to access medical, research, or patient information. Lastly, patient families have poor access to cutting-edge medical and scientific expertise that will inform their understanding of the disorder. Therefore, we believe that there is an urgent need to hold this meeting. The proposed conference will bring together stakeholders with the primary goal of maximizing scientific resources by building collaborative approaches that are efficient and synergistic, thereby accelerating the identification of effective treatments. We have commitments from the leading clinicians and researchers studying SynGAP biology and the related human disorders. Importantly, the meeting will be run in conjunction with the major MRD5 patient support network, Bridge-the GAP (www.bridgesyngap.org), which will organize the attendance of several families with affected children. The symposium will include sessions related to MRD5 clinical genetics/patient phenotypes, Syngap1 neurobiology, common substrates in neurodevelopmental disorders, epilepsy genetics, translational approaches in RASopathies, and accelerating translation in rare genetic disorders. We anticipate the creation of impactful opportunities for junior investigators, including women and minorities, to participate in scientific exchange and to meet MRD5 patients and their families. Key outcomes expected from this meeting include: (i) networking and establishment of collaborative research and clinical outreach programs; (ii) generation of new ideas on the pathogenesis and possible treatment of MRD5; (iii) expansion of the MRD5 research and clinical community; and (iv) establishment of an international MRD5 research and clinical network to foster fully collaborative, multi-laboratory basic research and to encourage initiation of a patient registry and natural history study in order to advance patient care and treatment.